Multi-well plates and methods of use thereof

Abstract

There is provided plate equipped with a mechanism to facilitate determination of the amount of a fluid added to or removed from a well in the plate. Other embodiments are also described.

The invention claimed is: 
     
       1. A method comprising:
 at a first time, obtaining a baseline measurement of displacement of at least one well in a multi-well plate having disposed therein a displacement measuring assembly for measuring the displacement of at least one well in said plate in response a change in an amount of fluid in said at least one well, said baseline measurement being obtained via said displacement measuring assembly; 
 at a second time after said first time, measuring the displacement of said at least one well; and 
 on the basis of a change in displacement between said first and second times, calculating a change in the amount of fluid in said at least one well, 
 wherein at at least one of said first and second times, a detectable amount of fluid is present in said well, 
 wherein said multiwell plate comprises:
 a first substantially planar surface having a plurality of first apertures defined therein, 
 a second substantially planar surface substantially parallel to said first substantially planar surface, said second substantially planar surface being spaced from said first substantially planar surface, 
 a plurality of wells located substantially within said plate, each well having a second aperture associated with one of said first apertures defined in said first surface and in alignment therewith, each of said wells having a sidewall and a bottom, a major portion of each well extending from the vicinity of said first substantially planar surface toward said second substantially planar surface, each of said major portion of said wells being displaceable within the region between the first and second substantially planar surfaces away from said first substantially planar surface toward said second substantially planar surface; and 
 said displacement measuring assembly comprises at least one signal provider, functionally associated with said plurality of wells, capable of producing a signal in response to displacement of said major portion of said at least one said well (a) away from said first surface and (b) toward said first surface in the region between said first and second substantially planar surfaces, 
 
 wherein said first and second surfaces are spaced apart by a plurality of sidewalls extending between said first and second surfaces. 
 
     
     
       2. The method of  claim 1 , wherein said calculating said change in an amount of said fluid comprises calculating at least one of (a) a volume of said fluid added to said at least one well after said first time and before said second time; (b) a mass of said fluid added to said at least one well after said first time and before said second time; and (c) a volume and a mass of said fluid added to said at least one well after said first time and before said second time. 
     
     
       3. The method of  claim 1 , wherein said fluid has been added to said at least one well of said plate before said first time, the method further comprising removing fluid from said plate after said first time and before said second time. 
     
     
       4. The method of  claim 3 , wherein said calculating the change in an amount of said fluid in said at least one well between said first time and said second time comprises calculating at least one of (a) a volume of said fluid lost from said at least one well after said first time and before said second time; (b) a mass of said fluid lost from said at least one well after said first time and before said second time; and (c) a volume and a mass of said fluid lost from said at least one well after said first time and before said second time. 
     
     
       5. The method of  claim 1 , further comprising:
 periodically repeating said step of measuring the displacement of said at least one well at a second time; and 
 on the basis of a change in displacement between two said measurements of displacement, calculating a change in the amount of fluid in said at least one well during a period between said two said measurements of displacement. 
 
     
     
       6. The method of  claim 1 , wherein the signal provider is sufficiently sensitive to detect at least one of:
 a change of 300 microliters (μl), 250 μl, 200 μl, 150 μl, 100 μl, 75 μl, 50 μl, 45 μl, 40 μl, 35 μl, 30 μl, 25 μl, 20 μl, 15 μl, 10 μl, 5 μl, 4 μl, 3 μl, 2 μl, 1 μl, 0.5 μl of fluid, 0.3 μl of fluid, 0.2 μl of fluid, or 0.1 μl of fluid, in the volume of fluid in said at least one well; and 
 a change of 300 milligrams (mg), 250 mg, 200 mg, 150 mg, 100 mg, 75 mg, 50 mg, 45 mg, 40 mg, 35 mg, 30 mg, 25 mg, 20 mg, 15 mg, 10 mg, 5 mg, 4 mg, 3 mg, 2 mg, 1 mg, 500 micrograms (μg), 300 μg, 200 μg, or 100 μg in the mass of fluid in said at least one well. 
 
     
     
       7. The method of  claim 1 , further comprising detecting a temperature in at least one well. 
     
     
       8. The method of  claim 1 , wherein at least one well in said multi-well plate is removable therefrom. 
     
     
       9. The method of  claim 1 , wherein said fluid has been added to said at least one well of said plate before said first time. 
     
     
       10. The method of  claim 1  wherein said change in said amount of fluid is due to addition of fluid to said at least one well. 
     
     
       11. The method of  claim 1  wherein said change in the amount of fluid is due to loss of fluid from said at least one well. 
     
     
       12. The method of  claim 1 , wherein said at least one signal provider comprises a plurality of signal providers, each associated with one well of said plurality of wells; said major portion of each of said plurality of wells is independently displaceable away from said first surface; and each of said plurality of signal providers is capable of providing a signal in response to displacement of said majority portion of one of said plurality of wells associated therewith. 
     
     
       13. The method of  claim 1 , wherein the plate comprises at least one temperature sensor associated with at least one of said wells, said at least one temperature sensor being configured to provide a signal representing a temperature in said at least one well or in a vicinity thereof. 
     
     
       14. The method of  claim 1 , wherein the plate further comprising an electronic storage element for storage of at least one signal provided by said at least one signal provider. 
     
     
       15. A method comprising:
 at a first time, obtaining a baseline measurement of displacement of at least one well in a multi-well plate having disposed therein a displacement measuring assembly for measuring the displacement of at least one well in said plate in response a change in an amount of fluid in said at least one well, said baseline measurement being obtained via said displacement measuring assembly; 
 at a second time after said first time, measuring the displacement of said at least one well; and 
 on the basis of a change in displacement between said first and second times, calculating a change in the amount of fluid in said at least one well, 
 
       wherein at at least one of said first and second times, a detectable amount of fluid is present in said well,
 wherein said multi-well plate comprises:
 a first substantially planar surface having at least one first aperture defined therein; 
 a second substantially planar surface substantially parallel to said first substantially planar surface, said second substantially planar surface being spaced from said first substantially planar surface by a plurality of sidewalls extending between said first and second surfaces; 
 at least one well defined within said plate, said at least one well having a second aperture corresponding to and in alignment with one of said at least one first aperture, said at least one well having a sidewall and a bottom and said at least one well extending from said first substantially planar surface toward said second substantially planar surface, said at least one well being displaceable away from said first substantially planar surface; and 
 at least one signal provider, functionally associated with said at least one well, capable of producing a signal in response to displacement of said at least one well away from said first surface, 
 wherein each signal provider of said at least one signal provider includes:
 at least one flexible arm attached at a first end thereof to a support and at a second end thereof engage at least a portion of said at least one well; 
 at least one strain gauge mounted onto said at least one flexible arm and adapted to detect deflection of said at least one flexible arm; and 
 
 at least one electronic card, functionally associated with said at least one strain gauge, and adapted to correlate the detected deflection of said at least one flexible arm with a change in content of said at least one well causing said displacement of said at least one well away from said first surface.